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检索条件"任意字段=中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议"

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A proximity pabeling strategy reveals a new function of PAQR3 in ER-to-Golgi Transport

A proximity pabeling strategy reveals a new function of PAQR...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Qianqian Cao Yan Chen CAS Key Laboratory of Nutrition and Metabolism Institute for Nutritional SciencesShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesChinese Academy of Sciences

As a newly discovered tumor suppressor,PAQR3 is a Multifunctional *** identify the new potential functions,we applied a proximity labeling strategy exploiting APEX2-fused PAQR3 to biotinylate proteins around PAQR3 in living *** this approach to two different cell types identified 992 proteins,most of which participate in intracellular transport and location,indicating a new function of PAQR3 in ER-to-Golgi *** RUSH assay revealed that ER-to-Golgi trafficking is affected by *** vitro COPII vesicle formation assay revealed PAQR3 have no effect on the budding of COPII vesicles,while PAQR3 can capture COPII components SEC13/SEC13 to Golgi via the N-terminal of *** further used a rerouting and capture assay that fuses the C-terminal transmembrane domain of monoamine oxidase(MAO) to the N-terminal of PAQR3(1-71 amino acids,PAQR3 N71) to relocate PAQR3 N71 from Golgi to mitochondrial,and the Mitochondrial-localized PAQR3 captured COPII cargos to ***,this study uncovers a new function of PAQR3 in ER-to-Golgi transport that capturing SEC13/SEC13 to Golgi and thus tethering vesicles from ER.

关键词： Proximity-dependent labeling APEX2 PAQR3 Golgi COPII transport

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Iron Drives T Helper Cell Pathogenicity by Promoting RNA-Binding Protein PCBP1-Mediated Proinflammatory Cytokine Production

Iron Drives T Helper Cell Pathogenicity by Promoting RNA-Bin...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Zhizhang Wang Weijie Yin Lizhen Zhu Jia Li Yikun Yao Feifei Chen Mengmeng Sun Jiayuan Zhang Nan Shen Yan Song Xing Chang Shanghai Institute of Nutrition and Health Chinese Academy of Sciences Department of Cellular and Molecular Medicine University of California at San Diego

Iron deposition is frequently observed in human autoinflammatory diseases,but its functional significance is largely *** we showed that iron promoted proinflammatory cytokine expression in T cells,including GM-CSF and IL-2,via regulating the stability of an RNA-binding protein *** depletion or Pcbp1 deficiency in T cells inhibited GMCSF production by attenuating Csf2 30 untranslated region(UTR) activity and messenger RNA ***1 deficiency or iron uptake blockade in autoreactive T cells abolished their capacity to induce experimental autoimmune encephalomyelitis,an animal model for multiple ***,intracellular iron protected PCBP1 protein from caspase-mediated proteolysis,and PCBP1 promoted messenger RNA stability of Csf2 and Il2 by recognizing UC-rich elements in the 30 *** study suggests that iron accumulation can precipitate autoimmune diseases by promoting proinflammatory cytokine ***-binding protein-mediated iron sensing may represent a simple yet effective means to adjust the inflammatory response to tissue homeostatic alterations.

关键词： Autoimmune disease Iron GM-CSF PCBP1 Post-transcriptional regulation

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草鱼白细胞介素12受体的分离鉴定

草鱼白细胞介素12受体的分离鉴定

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者：邱兴阳尹里程冯诗雨周红电子科技大学生命科学与技术学院

哺乳动物中,白细胞介素12(Interleukin 12, IL-12)主要由活化的巨噬细胞、树突状细胞和中性粒细胞产生;其主要功能是促进T辅助细胞1(T helper cell 1,Th1)的分化和增殖,以及诱导T细胞或NK细胞分泌干扰素-gamma(Interferon-gamma,IFN-γ)... 详细信息

哺乳动物中,白细胞介素12(Interleukin 12, IL-12)主要由活化的巨噬细胞、树突状细胞和中性粒细胞产生;其主要功能是促进T辅助细胞1(T helper cell 1,Th1)的分化和增殖,以及诱导T细胞或NK细胞分泌干扰素-gamma(Interferon-gamma,IFN-γ),进而在先天免疫和获得性免疫中发挥重要作用。IL-12是一种异源二聚体细胞因子,由p35和p40两个亚基通过链间二硫键连接构成,而IL-12受体(IL-12R)由IL-12Rβ1(识别IL-12 p40亚基)和IL-12Rβ2(识别IL-12 p35亚基)两个亚基构成。由于硬骨鱼在进化过程中发生过特有的基因组复制事件,导致多拷贝基因的存在。因此,相比哺乳动物而言,硬骨鱼细胞因子功能分化更为复杂而特殊。事实上,多数硬骨鱼IL-12的两个亚基(p35和p40)均由多基因编码,提示可能存在多种IL-12异构体。有趣的是,与之对应的受体也可能存在多基因编码。我们的研究表明草鱼IL-12p35亚基的受体IL-12Rβ2存在至少两个基因拷贝,一个是与哺乳动物具有保守邻位基因的IL-12Rβ2.a,另一个是单独存在于鱼类中的IL-12Rβ2.b,虽然两个基因的基因组定位不一样,但是从两者的结构域预测分析上来看,在胞外区都具有三个Ⅲ型纤连蛋白(FN3)结构域,即较高的结构相似性。而草鱼IL-12p40亚基的受体IL-12Rβ1存在两种剪接体形式,其中一个为完整转录子;另外一个剪接体中12号外显子缺失,而12号外显子所对应编码的氨基酸序列可以形成Ⅲ型纤连蛋白(FN3)结构域,此结构域是结合配体和信号转导的基础,可能会影响与IL-12的结合。现在上述受体及其异构体的真核表达质粒都已构建,准备将其转染进草鱼肾成纤维细胞中验证其功能。开展草鱼IL-12受体异构体的研究,有利于揭示鱼类特有的多基因编码导致的细胞因子功能分化的机制。

关键词：草鱼 IL-12受体基因组复制多拷贝基因剪接体

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Structural basis of highly specific interaction between Nephrin and MAGI1 in slit diaphragm assembly and signaling

Structural basis of highly specific interaction between Neph...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Zhuangfeng Weng Yuan Shang Zeyang Ji Fei Ye Lin Lin Rongguang Zhang Jinwei Zhu State Key Laboratory of Molecular Biology CAS Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences University of Chinese Academy of Sciences School of Life Science and Technology Shanghai Tech University Division of Life Science State Key Laboratory of Molecular Neuroscience Hong Kong University of Science and Technology

Slit diaphragm(SD) is a specialized adhesion junction between the opposing podocytes,establishing the final filtration barrier to prevent passage of proteins from the capillary lumen into the urinary *** is the key structural and signaling adhesion molecule prominently expressed in *** contains an evolutionally conserved atypical PDZ-binding motif(PBM),which has been reported to bind to a verity of proteins in *** mutations in the gene lacking the intact PBM have been associated with glomerular ***,the molecular basis of Nephrin-PBM-mediated protein complexes is still ***,we systematically investigated the interactions between Nephrin-PBM and PDZ domain-containing proteins in SD and showed that Nephrin-PBM specifically binds to MAGI1,but not *** complex structure of MAGI1-PDZ3/Nephrin-PBM reveals that the Gly at-3 position of Nephrin-PBM is the determining feature for MAGI1-PDZ3 recognition,which is in sharp contrast with the typical PDZ/PBM binding mode.A single mutation within MAGI2 results in a gain-of-function mutation for Nephrin-PBM ***,based on our structural analysis,we developed a highly efficient inhibitory peptide capable of specifically blocking the Nephrin/MAGI interaction,which may serve as a useful tool for investigating the functions of the interaction in *** study also provide possible explanations for the diseases caused by the mutations of NPHS1.

关键词： nephrin nephrotic syndrome glomerular filtration barrier cell adhesion

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Poly(C) Binding Proteins Regulate the Period of Circadian Clocks

Poly(C) Binding Proteins Regulate the Period of Circadian Cl...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Ming Wang Yaling Wu Na Liu Dapeng Ju Musheng Zeng Eric.Erquan Zhang Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China National Institute of Biological Sciences Anhui Province Key Laboratory of Biological Macro-Molecules Research Department of Biochemistry and Molecular BiologyWannan Medical College

Circadian rhythms are endogenous,entrainable,rough 24 h oscillations that coordinate daily changes in physiology and *** oscillations exist widely in most organisms and are governed by the internal time-keeping systems called circadian *** core mechanism of circadian clocks at the molecular level has been considered to be a transcription/translation feedback loop(TTFL) model which consists of positive and negative *** addition to the core TTFL loop,there are several additional ***,amplitude and phase are three key properties of a circadian *** these properties,period is the most stable *** studies including our own indicate that the stability,phosphorylation and nuclear localization of cryptochrome(CRY) are related to circadian *** the data of a previous genome-wide RNAi screen,we identified several poly(C) binding proteins,as candidates for clock *** current study shows that some poly(C) binding proteins regulate the period of circadian clocks by directly interacting with CRY,thereby influencing the operation of TTFL *** next,we plan to further investigate more detailed mechanism(s) on how poly(C) binding proteins regulate the circadian period.

关键词： poly(C) Circadian Period

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1-(5-Bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] inhibits MMP-9 expression by regulating NF-κB and MAPKs signaling pathways in HT1080 human fibrosarcoma cells

1-(5-Bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] inhibits...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Fang Gong YuanYuan Zhang JiaChao Lin ChengYong Li ChunXia Zhou PengZhi Hong BoMi Ryu Zhong-Ji Qian College of Food Science and Technology Guangdong Ocean University College of Chemical and Environmental Guangdong Ocean University Shenzhen Institute of Guangdong Ocean University Department of Marine Life Sciences Jeju National University

Hippocampus is a traditional medicine in China,which can be used for treating tumors,aging,fatigue,thrombosis,inflammation,hypertension,prostatic hyperplasia and other diseases.1-(5-Bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] from seahorse(Hippocampus kuda Bleeler) has been shown to suppress pro-inflammatory *** present study,SE1 potently inhibited gelatin digestion by MMP-9 induced by phorbol 12-myristate 13-acetate(PMA) and migration of human fibrosarcoma HT1080 cells in dose ***,western blot analysis and immunofluorescence analysis have been studied on MAPKs(ERK1/2,p38 kinase and JNK) and NF-κB(p65 and IκB),which refer to the clear molecular *** results indicated that SE1 significantly suppressed the phosphorylation of mitogen-activated protein kinases(MAPK: p38 kinase and JNK) and NF-κ***,molecular docking result showed SE1 interacts with TYR245 and HIS226 of MMP-9 by hydrogen bond and Pi-Pi bond to suppress MMP-9 *** data suggested that the SE1 may possess therapeutic and preventive potential for the treatment of MMP-9 related disorders.

关键词： Hippocampus SE1 Anti-metastatic MMP-9 MAPKs NF-κB molecular docking

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A Novel Strategy to Block NF-κB Signaling Pathway by Preventing IKKβ Activation

A Novel Strategy to Block NF-κB Signaling Pathway by Preven...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Hongbo Liu Hao Liang Hu Meng Xiaobing Deng Xiaoling Zhang Luhua Lai Peking-Tsinghua Center for Life Sciences Peking University BNLMS State Key Laboratory for Structural Chemistry of Unstable and Stable SpeciesCollege of Chemistry and Molecular EngineeringPeking University Center for Quantitative Biology Peking University

Transcription factor NF-κB plays a key role in various biological processes in ***-κB misregulation is involved in a variety of diseases such as chronic inflammation and *** I kappa B kinase β(IKKβ) is one of the primary regulators of NF-κB *** all of the known IKKβ inhibitors interact with the IKKβ active form and suffer from poor *** this work,we attempted to design inhibitors that can bind to the IKKβ inactive form and block its activation and the downstream NF-κB *** identified a potential allosteric site between the kinase domain(KD) and ubiquitinlike domain(ULD) of human IKKβ in the inactive conformation and subjected it to virtual screening for allosteric inhibitors from a chemical *** with experiment assays,we identified one compound 124 that specifically targets the IKKβ inactive *** cells upon TNFα stimulation,124 inhibited IκBα phosphorylation and NF-κB transcriptional activity for reporter gene with an IC50 of 35 μM via decreasing the phosphorylation level of Ser177/181 on IKKβ and blocking its *** dynamics simulations demonstrated that 124 binds to the pocket between KD and ULD in the inactive conformation of IKKβ rather than the active *** the first allosteric inhibitor that prevents IKKβ activation,124 provides a good starting point for further inhibitor discovery and a probe for IKKβ enzyme cycle and regulatory mechanism *** the IKKβ inactive conformation provides a novel strategy for the development of IKKβ inhibitors to block NF-κB signaling pathway.

关键词： NF-κB IKKβ Allosteric inhibitor

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Accurate and high-throughput, targeted quantification of CpG methylation without DNA extraction and bisulfite treatment

Accurate and high-throughput, targeted quantification of CpG...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Ya Ling Zhao Jun Zhou Zhi Zheng Dept.of Biochemistry and Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Science and School of Basic MedicinePeking Union Medical College

DNA methylations at specific CpG loci have been increasingly utilized as biomarkers for cancer *** multistep procedures of methylation assay such as DNA extraction,bisulfite conversion can decreased sensitivity and accuracy of *** we described a highly reproducible,endonuclease-based,quantitative and high throughput CpG methylation assay that does not involve DNA extraction and bisulfite conversion,with an ELISA-like workflow on one 96-well *** DNA lysed from blood sample is captured directly to 96-well plate by sandwich hybridization,the ligation products are treated with methylation-sensitive restriction endonuclease,which will cleave at specific unmethylated-cytosine residues while leaving the methylated ones *** buffer change,PCR amplification is performed with a universal *** methylation percentage levels are quantified via delta Cq with real-time *** showed the capture efficiency of our assay was close to 100%.We also observed the significantly better sensitivity of our extraction-free assay than using extracted DNA from the same amount of *** DNA samples with methylation levels range from 0%–100%,a linear regression analysis revealed quantitative and reproducible recovery across the entire methylation *** a significantly simplified procedure and a much higher throughput,our assay efficiently offered overall better accuracy of the measured methylation percentage values than obtained from methylight and gold standard pyrosequencing of the same *** feasibility of multiplex quantitative CpG methylation assessment using MOLDITOF mass spectrometry will alsobe *** no need for nucleic acid purification and bisulfate conversion,our method provides an accurate quantitative CpG methylation assay suitable for high-throughput applications.

关键词： CpG methylation Quantification Accurate High-throughput

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Identification, Characterization and Functional Investigation of Circular RNAs in SVZ of Adult Rat Brain

Identification, Characterization and Functional Investigatio...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Fang Xie Yun Zhao Shi-Da Wang Jing Ma Liang Zhang Xue Wang Ling-Jia Qian Institute of Military Cognitive and Brain Sciences Academy of Military Medical Sciences

Adult neural stem cells(NSCs) are able to self-renew and generate new neural *** regulators of NSCs is significant for the development of NSC-based therapies for neurodegenerative diseases and brain ***,circular RNAs(circRNAs) have been characterized in various cell lines and brain tissues,and found to participate in multiple biological ***,the expression pattern of circRNAs in adult NSCs is still ***,the subventricular zone(SVZ) of the lateral ventricle was isolated as the niche of NSCs in adult rat brain for RNA *** the characteristics of circRNAs profiling in both SVZ and cerebral cortex were also *** a result,29049 and 31975 circRNAs were identified in SVZ and cortex,*** them,41 were SVZ-specific and 48 were cortex-specific.467 circRNAs were also found to express predominately in SVZ,while the cortex had other 423 regnant *** ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses revealed that the SVZ-specific circRNAs have closely relationship with the regulation of NSC expansion and NSC-niche interaction,while the other differentially expressed circRNAs might be involved in neural cellular construction and nerves system ***,the interactions between circRNAs and microRNAs were also explored,and the result showed that one SVZ-specific circRNA was capable to competitively bind miR-138-5 p as a potential derepressive regulator in NSCs ***,our work has laid the foundations to decipher regulation mechanisms of circRNAs in adult NSCs and to develop circRNAs as novel biomarkers for adult NSCs.

关键词： circular RNA neural stem cell subventricular zone RNA-seq microRNA

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Multifaceted functions of a human aminoacyl-tRNA synthetase in protein synthesis and beyond

Multifaceted functions of a human aminoacyl-tRNA synthetase ...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Ru-Juan Liu Tao Long Hao Li En-Duo Wang State Key Laboratory of Molecular Biology CAS Center for Excellence in Molecular Cell ScienceInstitute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of Sciences School of Life Science and Technology ShanghaiTech University

Aminoacyl-tRNA synthetases(aaRSs) are prominently known for their conventional function of generating aminoacylt RNAs to provide material for protein ***,beyond protein synthesis,aaRSs have been shown to exhibit other essential nonconventional functions independent of their catalytic *** human cytosolic leucyl-tRNA synthetase(LeuRS) is one of the most multifaceted aaRS: beside the activity of catalyzing the covalently ligation of leucine to tRNALeus,it could also hydrolyze the mischarged tRNAs,meanwhile,it forms a big MSC complex with other seven aaRSs and scaffold proteins in vivo;most intriguingly,LeuRS could regulated the activity of mTOR pathway which is essential for cell nutrient sensing and active in cancer development;even more,the overexpression of LeuRS was found to be closely related with colon cancer makes LeuRS a convincing target for anti-tumor drug *** structure of LeuRS from eukaryote is remaining unclear for years due the complexity of multi-domains and dynamic property of *** we solve the fulllength structure of human cytosolic LeuRS(hcLeuRS),which contains 1176 amino acid residues with four domains and several connection ***,the architecture of hcLeuRS is similar to LeuRS from archrea but different to that from bacteria distinguished by the insertion site of editing CP1 *** interactions between hcLeuRS and tRNA or the mTOR pathway proteins were studied by biophysical *** on the structure,we further investigate the binding affinity of different series of compounds targeting to either the aminoacylation domain,or the editing domain or the protein interaction *** also solved the complex structure of hcLeuRS with some of the ***,our study provide structural basis for both understanding the multifaceted functions of hcLeuRS and also for drug development targeting to hcLeuRS.

关键词： Aminoacyl-tRNA synthetases multifaceted functions structure drug development

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